The long-term goal of this research is to advance the understanding of the neuro-humoral regulation of central nervous system function and is presently focused upon factors controlling cyclic AMP metabolism in CNS tissue. As a result of the inexplicable effects of 40mM K Cl upon the accumulation of cyclic AMP in guinea pig cerebral cortical slices, it is proposed to search for, and to characterize as yet unidentified humoral agents contained in brain tissue. It is further proposed to investigate mechanisms responsible for the potentiative interaction between maximal amounts of adenosine and histamine or norepinephrine. As part of the experimental approach, recently developed immunofluorescent histochemical and radioimmunologic techniques will be applied to the determination of regional or localized patterns of responsiveness in brain slices incubated with various agonists. Another approach will involve investigation of the patterns of responsiveness to biogenic amines, adenosine, depolarizing agents and combinations thereof in the cerebral cortex and cerebellum of inbred strains of guinea pig and rabbit.